Institution
Rush University Medical Center
Healthcare•Chicago, Illinois, United States•
About: Rush University Medical Center is a healthcare organization based out in Chicago, Illinois, United States. It is known for research contribution in the topics: Population & Dementia. The organization has 13915 authors who have published 29027 publications receiving 1379216 citations. The organization is also known as: Rush Presbyterian St. Luke's Medical Center.
Topics: Population, Dementia, Transplantation, Cognitive decline, Health care
Papers published on a yearly basis
Papers
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TL;DR: Irrespective of ancestry, early age at diagnosis and a family history of breast and ovarian cancer are the most powerful predictors of mutation status and should be used to guide clinical decision making.
Abstract: ContextTen years after BRCA1 and BRCA2 were first identified as major breast cancer susceptibility genes,
the spectrum of mutations and modifiers of risk among many ethnic minorities
remain undefined.ObjectivesTo characterize the clinical predictors, spectrum, and frequency of BRCA1 and BRCA2 mutations in an
ethnically diverse high-risk clinic population and to evaluate the performance
of the BRCAPRO statistical model in predicting the likelihood of a mutation.Design, Setting, and ParticipantsComparative analysis of families (white, Ashkenazi Jewish, African American,
Hispanic, Asian) with 2 or more cases of breast and/or ovarian cancer among
first- and second-degree relatives. Families were identified at US sites between
February 1992 and May 2003; in each family, the individual with the highest
probability of being a mutation carrier was tested.Main Outcome MeasuresFrequency of BRCA1 and BRCA2 mutations and area under the receiver operating characteristic curve
for the BRCAPRO model.ResultsThe mutation spectrum was vastly different between families of African
and European ancestry. Compared with non-Hispanic, non-Jewish whites, African
Americans had a lower rate of deleterious BRCA1 and BRCA2 mutations but a higher rate of sequence variations
(27.9% vs 46.2% and 44.2% vs 11.5%; P<.001 for
overall comparison). Deleterious mutations in BRCA1 and BRCA2 were highest for Ashkenazi Jewish families (69.0%).
Early age at diagnosis of breast cancer and number of first- and second-degree
relatives with breast and ovarian cancer were significantly associated with
an increased likelihood of carrying a BRCA1 or BRCA2 mutation. In discriminating between mutation carriers,
BRCAPRO performed as well in African American families as it did in white
and Jewish families, with an area under the curve of 0.77 (95% confidence
interval, 0.61-0.88) for African American families and 0.70 (95% confidence
interval, 0.60-0.79) for white and Jewish families combined.ConclusionsThese data support the use of BRCAPRO and genetic testing for BRCA1 and BRCA2 mutations in the
management of high-risk African American families. Irrespective of ancestry,
early age at diagnosis and a family history of breast and ovarian cancer are
the most powerful predictors of mutation status and should be used to guide
clinical decision making.
239 citations
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TL;DR: The results suggest that difficulty in identifying familiar odours in old age is partly due to the accumulation of neurofibrillar pathology in central olfactory regions.
Abstract: Background: Olfactory dysfunction is common in old age, but its basis is uncertain. Objective: To test the hypothesis that difficulty in identifying odours in old age is related to the accumulation of Alzheimer’s disease pathology. Methods: As part of the Rush Memory and Aging Project, participants completed the 12-item Brief Smell Identification Test, a standard measure of odour identification. During a mean (standred deviation (SD)) of 2.2 (1.2) years of follow-up (range 0.2–4.9), 166 people died, with brain autopsies performed on 129 (77.7%) people and neuropathological examinations completed on 77 (mean (SD) age at death 87.5 (5.9) years; median postmortem interval 6.1 h). From a uniform postmortem examination of multiple brain regions, summary measures of plaque and tangle pathology were derived on the basis of silver staining, and those of amyloid β burden, tangle density and Lewy bodies on the basis of immunohistochemistry. Results: Odour identification performance ranged from 0 to 12 correct (mean (SD) 8.0 (2.6)). In analyses adjusted for age, sex and education, a composite measure of plaques and tangles accounted for >12% of the variation in odour identification. The association remained after controlling for dementia or semantic memory. Density of τ tangles was inversely related to odour identification. A similar effect for amyloid burden was attenuated after controlling for tangles. The association with odour identification was robust for tangles in the entorhinal cortex and CA1/subiculum area of the hippocampus, but not for tangles in other cortical sites. Lewy bodies, identified in 12.5%, were not related to odour identification, probably partly due to to their relative infrequency. Conclusion: The results suggest that difficulty in identifying familiar odours in old age is partly due to the accumulation of neurofibrillar pathology in central olfactory regions.
239 citations
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TL;DR: The potential actions of various blood constituents on joint components that culminate in the development of hemophilic arthropathy are reviewed.
239 citations
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TL;DR: The efficacy of appropriately timed bright light exposure and exogenous melatonin administration for producing circadian adaptation to night work and the impact of individual differences on possible circadian interventions and issues associated with the use of bright light interventions in the field are discussed.
239 citations
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TL;DR: No by itself is not cytotoxic to cultured chondrocytes and can even be protective under certain conditions of oxidative stress, and selective ROS scavengers protected against cell death caused by either SIN-1 or ONOO-; however, no protection could be afforded against the cytotoxicity of SNP with any of the ROS scavenger tested.
Abstract: Objective
Chondrocyte cell death, possibly related to increased production of endogenous nitric oxide (NO), has been observed during the pathogenesis of osteoarthritis and rheumatoid arthritis. The purpose of this study was to investigate the potential role of NO in causing chondrocyte cell death and to determine the contribution of other reactive oxygen species (ROS).
Methods
Cell death and cytotoxicity were evaluated in human articular chondrocytes in response to various NO donor compounds with and without agents that stimulate or inhibit the production of additional ROS using both the alginate bead and the monolayer culture systems. Cell death was quantified by a total cell count with fluorescent labels, and cytotoxicity was measured as a function of cellular NADH- and NADPH-dependent dehydrogenase activity. To determine if the redox status of the chondrocyte could influence the observed effect of NO, cells were preincubated for 24 hours in L-cystine– and glutathione (GSH)–depleted media to reduce intracellular GSH levels, a major defense mechanism against oxidative stress. Apoptosis was analyzed with the quantification of histone-associated DNA fragments.
Results
Treatment of chondrocytes with peroxynitrite (ONOO−), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) resulted in apoptotic cell death at concentrations of 0.5 mM, 1.0 mM, and 0.5 mM, respectively. In contrast, treatment of chondrocytes with diazeniumdiolates (or the “NOC” compounds, NOC-5 and NOC-12) at concentrations as high as 2.0 mM did not cause cell death. Furthermore, NOC-5 and NOC-12, at all concentrations tested (0.125–2.0 mM), could prevent cell death caused by oxidative stress. Selective ROS scavengers protected against cell death caused by either SIN-1 or ONOO−; however, no protection could be afforded against the cytotoxicity of SNP with any of the ROS scavengers tested.
Conclusion
These results show that NO by itself is not cytotoxic to cultured chondrocytes and can even be protective under certain conditions of oxidative stress. Chondrocyte cell death from NO occurs under conditions where other ROS are also generated.
239 citations
Authors
Showing all 14032 results
Name | H-index | Papers | Citations |
---|---|---|---|
John Q. Trojanowski | 226 | 1467 | 213948 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Luigi Ferrucci | 193 | 1601 | 181199 |
David A. Bennett | 167 | 1142 | 109844 |
Todd R. Golub | 164 | 422 | 201457 |
David Cella | 156 | 1258 | 106402 |
M.-Marsel Mesulam | 150 | 558 | 90772 |
John D. E. Gabrieli | 142 | 480 | 68254 |
David J. Kupfer | 141 | 862 | 102498 |
Clifford B. Saper | 136 | 406 | 72203 |
Pasi A. Jänne | 136 | 685 | 89488 |
Nikhil C. Munshi | 134 | 906 | 67349 |
Martin B. Keller | 131 | 541 | 65069 |
Michael E. Thase | 131 | 923 | 75995 |
Steven R. Simon | 129 | 1090 | 80331 |